Racial Differences in Oncogene Mutations Detected in Early-Stage Low-Grade Endometrial Cancers

Abstract

Objective To describe the pattern and frequency of oncogene mutations in white and African American (AA) women with endometrial cancer, and to determine if racial differences in oncogene mutations exist among women with pathologically similar tumors. Methods Endometrial cancer patients from a large, urban hospital were identified through medical records, and representative formalin fixed paraffin embedded tumor blocks were retrieved. The study sample included 150 patients (84 AA) who underwent total abdominal hysterectomy for endometrial cancer. The Sequenom MassARRAY system and the OncoCarta Assay v1.0 (Sequenom), were employed to test for 238 mutations in 19 common oncogenes. Chi-square tests and Fisher’s exact tests were used to assess differences in distribution of variables by race and oncogene mutation status. Results There were 20 mutations identified in 2 oncogenes (PIK3CA and KRAS) in tumors from 19 women (12.7%). The majority of mutations were found in PIK3CA (16/20). Thirteen percent of endometroid tumors harbored mutations (11 PIK3CA and 2 KRAS), as did 29% of the Malignant Mixed Mullerian tumors (3 PIK3CA and 1 KRAS). There were no observed mutations in serous, clear cell, or mucinous tumor types. Among low grade endometrioid cancers, tumors from AA patients were significantly associated with harboring either a KRAS or PIK3CA mutation (p=0.04), with 7 PIK3CA mutations and all 4 KRAS mutations identified in AA women. Conclusions This study provides preliminary evidence that oncogene mutation frequency of some subtypes of histologically similar endometrial carcinoma differ by race. Additional studies are needed to further explore this phenomenon in patients with endometrial carcinoma.

Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas

“…Microsatellite instability (MSI) is three times more common in the tumors of Caucasians compared to BoAA women [ 9 ]; whereas BoAA women have higher incidence of TP53 mutations [ 10 ], thought to be related to higher incidence of Type 2 tumors in these patients. Racial differences have also been seen with PIK3CA and KRAS mutations being seen more frequently in BoAA women as compared to Caucasian women in low-grade endometrioid EC [ 11 ]. Unlike the breadth of knowledge regarding the comparison between BoAA and Caucasian women, much less is known about other ethnic minority groups, for example, Asian.…”

Racial Differences in Esophageal Squamous Cell Carcinoma: Incidence and Molecular Features

“…Genome sequencing of liver cancer found that AXIN1 was more frequently mutated in patients with HBV infection, while mutations of its downstream gene CTNNB1 majorly occurred in HCV-associated cases [8, 9]. Racial diversity of endometrial cancers [10] and non-small-cell lung cancer [11] were investigated by comparing somatic mutations in common cancer genes. Their results suggested that the mutation frequencies of some genes vary according to race, which could benefit cancer diagnosis and treatment.…”

Lumbee Native American ancestry and the incidence of aggressive histologic subtypes of endometrial cancer

“…However there was a non-significant trend toward a difference in both high grade ( p = 0.07) and high-risk histology ( p = 0.08) when all 3 cohorts were compared, with Lumbees having a frequency of high-risk cancers between that of Whites and Blacks. Prior studies have demonstrated that Blacks have a higher rate of high-risk endometrial cancer subtypes and a poorer prognosis than Whites ( Cote et al, 2012a , Cote et al, 2012b , Sherman and Devesa, 2003 , Maxwell et al, 2006 , Santin et al, 2005a , Santin et al, 2005b , Setiawan et al, 2007 , Ueda et al, 2008 ). While we did not demonstrate poor cancer outcomes in the Lumbee cohort, the small size of our study likely limits our ability to assess this.…”